title: Aldosterone induces myofibroblastic transdifferentiation and collagen gene expression through the Rho-kinase dependent signaling pathway in rat mesangial cells.
abstract: There is accumulating evidence indicating the role of aldosterone in the pathogenesis of hypertension and renal injury. In this study, we investigated the role of the Rho-kinase dependent signaling pathway in aldosterone-induced myofibroblastic transdifferentiation and collagen gene expression in rat mesangial cells (RMCs). Stimulation with aldosterone (1 nmol/L) significantly increased phosphorylation of myosin phosphatase target subunit-1 (MYPT-1), a marker of Rho-kinase activity, with a peak at 20 min in RMCs. Pre-incubation with a selective mineralocorticoid receptor antagonist, eplerenone (10 micromol/L), or a specific Rho-kinase inhibitor, Y27632 (10 micromol/L), attenuated the aldosterone-induced increase in MYPT-1 phosphorylation. Aldosterone also induced hypertrophy in RMCs, accompanied by an increase in actin polymerization and expression of alpha-smooth muscle actin (alpha-SMA), a myofibroblastic transdifferentiation marker. Collagen type I, III and IV mRNA levels were also increased with aldosterone stimulation. Pre-treatment with eplerenone or Y27632 prevented the aldosterone-induced cell hypertrophy, actin polymerization, the increase in alpha-SMA expression and the increases of collagen type I, III, IV mRNA levels in RMCs. These results suggest that aldosterone-induced mesangial cell hypertrophy is associated with cell transformation, leading to an increase in collagen gene expression via the Rho-kinase dependent signaling pathway.
authors.affiliation: Department of Pharmacology Faculty of Medicine, Kagawa University, 761-0793, Japan.
authors.forename: Suwarni
authors.initials: S
authors.lastname: Diah
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nagai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Liu
authors.initials: L
authors.lastname: Gang
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Mas R W Abdul
authors.initials: MR
authors.lastname: Hamid
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamiya
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D054338:Cell Transdifferentiation / Q000187:drug effects* / Q000235:genetics; D003094:Collagen / Q000235:genetics*; D000077545:Eplerenone; D005786:Gene Expression Regulation / Q000187:drug effects; D006984:Hypertrophy; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D024510:Muscle Development / Q000187:drug effects* / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D000577:Amides; D000451:Mineralocorticoid Receptor Antagonists; D011725:Pyridines; D018161:Receptors, Mineralocorticoid; C108830:Y 27632; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D003094:Collagen; D054460:rho-Associated Kinases